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Hematology Basics & Hematopoiesis HEMATOLOGY What is it? Encompasses: Skill, Art, Instinct Relationships BM:circulation Plasma:RBC Hgb:RBC What Will I Learn? Students find Hematology difficult because it requires you to think in a new way. Begin with limited knowledge: Given Facts and you must be able to answer “WHY” Given images and you must be able to recognize and classify This Course Hematology I – MLTS 207 Intro Red Cells Hematology II – MLTS 208 White Cells Coagulation Our Tool Safety First Standard Precautions PPE Hand washing Proper disposal Proper cleaning Know what to do in case of an emergency Fire Spill Needle stick QA vs QC Quality Assurance Comprehensive Preanalytical – Analytical - Post-analytical Ensures reliable patient results = positive outcome Quality Control is Analytical only – focuses on actual measurement of the analyte Quality Control Standards / Calibrators Controls Statistical quality control system Normals AKA Reference ranges Plt 150 – 450 X 103/ul Unique to analyte, method, instrument and patient population Delta Check Critical Values Blood Basics Average blood volume 4 – 6 liters Blood pH = 7.35 – 7.45 Components of whole blood 55% plasma - 44% RBCs - 1% WBCs and platelets (buffy coat) Red Blood Cell (Erythrocyte or RBC) White Blood Cell (Leukocyte or WBC) Platelets (Thrombocyte) Plasma is 91.5% water and 8.5% solutes Reference Ranges (patient normals) RBC 4.2 – 5.4 X 1012/L (106/ul) females 4.7 – 6.1 X 1012/L (106/ul) males WBC 5 – 10 X 109/L (103/ul) Platelets 150 – 450 X 109/L (103/ul) Blood Smears (Slides) Cells evaluated in an area where red cells are almost touching but do not overlap Smears can be made by hand or mechanically Smears are stained with Wright’s stain Smear is examined on 100X using oil to evaluate RBC morphology RBC Morphology Red cells are biconcave disk that are 7 – 8 um in diameter with a volume - 90fL (femtoliters) When stained they appear as: Circular cells with distinct smooth margins Dull pinkish hue Area of central pallor Fairly uniform in size No nucleus or inclusions Platelet Morphology Platelets are 2 – 4um in diameter and discoid shaped they contain reddish-purple granules in a small amount of bluish cytoplasm and have no nucleus Leukocytes Segmented neutrophils - AKA segs or PMN Band neutrophils Eosinophils Basophils Lymphocytes Monocytes Hematopoiesis Definition? Daily Production Quotas RBCs – 3 billion WBCs – 1.5 billion Plts – 2.5 billion Your body can: Constantly supply mature blood cells for circulation Mobilize Bone Marrow to increase production of a particular type of blood cell Compensate for decreased hematopoiesis by providing hematopoietic sites outside the BM The Beginning All blood cells are the progeny of hematopoietic pluriopotential stem cell In adults these are found in the bone marrow. Why? Monophyletic Theory A common precursor cell, the pluripotential stem cell, which under the influence of certain factors gives rise to each of the principle blood cell lines Cytokines - Pretty much universally accepted today based on clinical and experimental evidence and started with mice in 1961 Based on this theory, hematopoietic cells may be divided into 3 cellular catagories dependant on maturity 1 Multipotential stem cell able to self-renew and to differentiate into all blood cell lines 2 Committed progenitor cell destined to develop into distinct cell lines 3 Mature cells with specialized functions which have lost the capability to proliferate Hematopoietic Stem Cell Most important characteristic – must self renew Ability to differentiate into commited progenitor cells of lymphoid or myloid lineages Maturation Process (p.20) Hematopoiesis From Coception to Adulthood (p.16) Yolk Sac (embryonic hemoglobin) Begins 2 -3 weeks after fertilization and ceases after 8 – 10 weeks Fetal Liver (fetal hemoglobin) Production from about 2 – 7 months Liver is main site but spleen, thymus, lymph nodes, and kidney are also involved Bone Marrow – called medullary hematopoiesis Begins to function in 3rd month of gestation Primary site by the end of 5th month of gestation and continues after birth and throughout adulthood Children distal long bones Adults axial bones Extramedullary Hematopoiesis is hematopoiesis outside bone marrow Not a normal occurrence after 5th month of gestation Happens in certain disorders Occurs in liver and spleen Erythropoiesis Definition? Mature erythrocytes carry oxygen from the lungs to tissue where it is exchanged for CO2 Erythropoietin (a cytokine) Hormone produced by the kidney Stimulates red cell production Secreted daily in small amounts Kidney will sense hypoxia and secrete more if needed What happens when more EPO is secreted by the kidneys? Development of Red Cell Reduction in cell volume Condensation of chromatin (Loss of nucleoli) Decrease in N:C ratio (less nucleus – more cytoplasm) Decrease of RNA in cytoplasm Increased hemoglobin synthesis – to a point cell turns from blue to red Developmental Stages (images p33 - 35) Rubriblast (Pronormoblast) Each produces 8 – 16 mature red cells Stage where hemoglobin synthesis begins Prorubricyte (Basophilic Normoblast) Rubricyte (Polychromatophilic Normoblast) Last stage capable of division Large amounts of hemoglobin synthesized at this stage Metarubricyte (Orthochroimatophilic Normoblast) Nucleated Red Blood Cell (NRBC) seen on peripheral smear Reticulocyte (Polychromatophilic Erythrocyte) Non-nucleated (nucleus extruded) Contains residual RNA and mitochondria which gives cell bluish tinge with Wright’s stain Last stage to synthesize hemoglobin Part of this phase occurs in the bone marrow, later part takes place in circulating blood Mature Erythrocyte Stains pink because of large amount of hemoglobin No RNA or mitochondria = no synthesizing of proteins or lipids Normal lifespan 120 days Have You Seen Your Spleen Fist shaped organ located on the left side under the rib cage Blood filled organ consisting of Red pulp – red cell filtration Cull old or abnormal RBCs (Reticuloedothelial System) Pit RBC inclusions Remove Antibodies - spherocytes White pulp – lymphocyte processing Marginal zone – WBC & Plt storage 1/3 population of each Bone Marrow not Bowel Movement One of the largest organs in the body Inside you find erythroid cells, myloid cells, and megakaryocytes in various stages of development – stem cells, fatty tissue, osteoclasts, etc. As you age marrow in long bones is replaced by fat Adult marrow in iliac crest and sternum. M:E ratio -Myeloid to erythroid ratio Normally 3-4:1 Why are there more myloid cells in the bone marrow and more RBCs in circulation?
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